| 1. |
- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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| 2. |
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| 3. |
- Abolhassani, H, et al.
(författare)
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Care of patients with inborn errors of immunity in thirty J Project countries between 2004 and 2021
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 1032358-
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Tidskriftsartikel (refereegranskat)abstract
- The J Project (JP) physician education and clinical research collaboration program was started in 2004 and includes by now 32 countries mostly in Eastern and Central Europe (ECE). Until the end of 2021, 344 inborn errors of immunity (IEI)-focused meetings were organized by the JP to raise awareness and facilitate the diagnosis and treatment of patients with IEI.ResultsIn this study, meeting profiles and major diagnostic and treatment parameters were studied. JP center leaders reported patients’ data from 30 countries representing a total population of 506 567 565. Two countries reported patients from JP centers (Konya, Turkey and Cairo University, Egypt). Diagnostic criteria were based on the 2020 update of classification by the IUIS Expert Committee on IEI. The number of JP meetings increased from 6 per year in 2004 and 2005 to 44 and 63 in 2020 and 2021, respectively. The cumulative number of meetings per country varied from 1 to 59 in various countries reflecting partly but not entirely the population of the respective countries. Altogether, 24,879 patients were reported giving an average prevalence of 4.9. Most of the patients had predominantly antibody deficiency (46,32%) followed by patients with combined immunodeficiencies (14.3%). The percentages of patients with bone marrow failure and phenocopies of IEI were less than 1 each. The number of patients was remarkably higher that those reported to the ESID Registry in 13 countries. Immunoglobulin (IgG) substitution was provided to 7,572 patients (5,693 intravenously) and 1,480 patients received hematopoietic stem cell therapy (HSCT). Searching for basic diagnostic parameters revealed the availability of immunochemistry and flow cytometry in 27 and 28 countries, respectively, and targeted gene sequencing and new generation sequencing was available in 21 and 18 countries. The number of IEI centers and experts in the field were 260 and 690, respectively. We found high correlation between the number of IEI centers and patients treated with intravenous IgG (IVIG) (correlation coefficient, cc, 0,916) and with those who were treated with HSCT (cc, 0,905). Similar correlation was found when the number of experts was compared with those treated with HSCT. However, the number of patients treated with subcutaneous Ig (SCIG) only slightly correlated with the number of experts (cc, 0,489) and no correlation was found between the number of centers and patients on SCIG (cc, 0,174).Conclusions1) this is the first study describing major diagnostic and treatment parameters of IEI care in countries of the JP; 2) the data suggest that the JP had tremendous impact on the development of IEI care in ECE; 3) our data help to define major future targets of JP activity in various countries; 4) we suggest that the number of IEI centers and IEI experts closely correlate to the most important treatment parameters; 5) we propose that specialist education among medical professionals plays pivotal role in increasing levels of diagnostics and adequate care of this vulnerable and still highly neglected patient population; 6) this study also provides the basis for further analysis of more specific aspects of IEI care including genetic diagnostics, disease specific prevalence, newborn screening and professional collaboration in JP countries.
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| 4. |
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| 5. |
- Wagner, L., et al.
(författare)
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Astrophysical S factor of the N 14 (p,γ) O 15 reaction at 0.4-1.3 MeV
- 2018
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Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 97:1
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Tidskriftsartikel (refereegranskat)abstract
- The N14(p,γ)O15 reaction is the slowest reaction of the carbon-nitrogen cycle of hydrogen burning and thus determines its rate. The precise knowledge of its rate is required to correctly model hydrogen burning in asymptotic giant branch stars. In addition, it is a necessary ingredient for a possible solution of the solar abundance problem by using the solar N13 and O15 neutrino fluxes as probes of the carbon and nitrogen abundances in the solar core. After the downward revision of its cross section due to a much lower contribution by one particular transition, capture to the ground state in O15, the evaluated total uncertainty is still 8%, in part due to an unsatisfactory knowledge of the excitation function over a wide energy range. The present work reports precise S factor data at twelve energies between 0.357 and 1.292 MeV for the strongest transition, capture to the 6.79-MeV excited state in O15, and at ten energies between 0.479 and 1.202 MeV for the second strongest transition, capture to the ground state in O15. An R-matrix fit is performed to estimate the impact of the new data on astrophysical energies. The recently suggested slight enhancement of the 6.79-MeV transition at low energy could not be confirmed. The present extrapolated zero-energy S factors are S6.79(0)=1.24±0.11 keV b and SGS(0)=0.19±0.05 keV b.
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| 6. |
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| 7. |
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| 8. |
- Ryvlin, Philippe, et al.
(författare)
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Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS) : a retrospective study
- 2013
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 12:10, s. 966-977
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Tidskriftsartikel (refereegranskat)abstract
- Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. Methods Between Jan 1,2008, and Dec 29,2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. Findings 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5.1 (95% CI 2.6-9.2) per 1000 patient-years, with a risk of 1.2 (0.6-2.1) per 10 000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. Interpretation SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time.
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| 9. |
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| 10. |
- Barnes, A. T., et al.
(författare)
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LEGO - II. A 3mm molecular line study covering 100 pc of one of the most actively star-forming portions within the Milky Way disc
- 2020
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 497:2, s. 1972-2001
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Tidskriftsartikel (refereegranskat)abstract
- The current generation of (sub)mm-telescopes has allowed molecular line emission to become a major tool for studying the physical, kinematic, and chemical properties of extragalactic systems, yet exploiting these observations requires a detailed understanding of where emission lines originate within the Milky Way. In this paper, we present 60'' (similar to 3pc) resolution observations of many 3mm-band molecular lines across a large map of the W49 massive star-forming region (similar to 100x100pc at 11kpc), which were taken as part of the 'LEGO' IRAM-30m large project. We find that the spatial extent or brightness of the molecular line transitions are not well correlated with their critical densities, highlighting abundance and optical depth must be considered when estimating line emission characteristics. We explore how the total emission and emission efficiency (i.e. line brightness per H-2 column density) of the line emission vary as a function of molecular hydrogen column density and dust temperature. We find that there is not a single region of this parameter space responsible for the brightest and most efficiently emitting gas for all species. For example, we find that the HCN transition shows high emission efficiency at high column density (10(22)cm(-2)) and moderate temperatures (35K), whilst e.g. N2H+ emits most efficiently towards lower temperatures (10(22)cm(-2); <20K). We determine XCO(1-0)similar to 0.3 x 10(20)cm(-2)(Kkms(-1))(-1), and alpha(HCN(1-0))similar to 30M(circle dot)(Kkms(-1)pc(2))(-1), which both differ significantly from the commonly adopted values. In all, these results suggest caution should be taken when interpreting molecular line emission.
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| 11. |
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| 12. |
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| 13. |
- Jarrett, Benjamin J.M., et al.
(författare)
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Experimental adaptation of native parasitoids to the invasive insect pest, Drosophila suzukii
- 2022
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Ingår i: Biological Control. - : Elsevier BV. - 1049-9644. ; 167
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Tidskriftsartikel (refereegranskat)abstract
- The spread of invasive pests is increasing due to greater global transportation and climate change-mediated range shifts. In a new community, these invasive species provide a novel resource that native predators or parasitoids can evolve to utilise. For invasive agricultural pests, this could provide top-down control; however, initial attack rates on invasive species in the wild are generally low. The potential for rapid adaptive evolution of native species to improve developmental success on invasive species is unknown. We address this by focusing on Drosophila suzukii, a polyphagous invasive pest, and two cosmopolitan Drosophila parasitoids found in North America prior to the arrival of D. suzukii (Pachycrepoideus vindemiae and Trichopria drosophilae). We experimentally evolved three replicate populations of both species on D. suzukii and the cosmopolitan D. melanogaster, a common host for both parasitoids. We found evidence that P. vindemiae increased developmental success by 88% (95% credible intervals = [−14%, 254%]) and T. drosophilae increased developmental success by 259% [38%, 711%] on D. suzukii after only three generations of selection, despite very low founding sizes of 2 and 30 wasps, respectively. These results demonstrate that rapid evolution of increased virulence is possible even from low genetic diversity, with implications for integrating evolutionary techniques into biological control of invasive species.
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| 14. |
- Jarrett, Benjamin J.M., et al.
(författare)
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Traits across trophic levels interact to influence parasitoid establishment in biological control releases
- 2022
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- A central goal in ecology is to predict what governs a species’ ability to establish in a new environment. One mechanism driving establishment success is individual species’ traits, but the role of trait combinations among interacting species across different trophic levels is less clear. Deliberate or accidental species additions to existing communities provide opportunities to study larger scale patterns of establishment success. Biological control introductions are especially valuable because they contain data on both the successfully established and unestablished species. Here, we used a recent dataset of importation biological control introductions to explore how life-history traits of 132 parasitoid species and their herbivorous hosts interact to affect parasitoid establishment. We find that of five parasitoid and herbivore traits investigated, one parasitoid trait—host range—weakly predicts parasitoid establishment; parasitoids with higher levels of phylogenetic specialization have higher establishment success, though the effect is marginal. In addition, parasitoids are more likely to establish when their herbivore host has had a shorter residence time. Interestingly, we do not corroborate earlier findings that gregarious parasitoids and endoparasitoids are more likely to establish. Most importantly, we find that life-history traits of the parasitoid species and their hosts can interact to influence establishment. Specifically, parasitoids with broader host ranges are more likely to establish when the herbivore they have been released to control is also more of a generalist. These results provide insight into how multiple species’ traits and their interactions, both within and across trophic levels, can influence establishment of species of higher trophic levels.
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| 15. |
- Kowal-Bielecka, Otylia, et al.
(författare)
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Update of EULAR recommendations for the treatment of systemic sclerosis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76, s. 1327-1339
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc.
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| 16. |
- Linder, Shelley, et al.
(författare)
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Limited gains in native parasitoid performance on an invasive host beyond three generations of selection
- 2022
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 15:12, s. 2113-2124
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Tidskriftsartikel (refereegranskat)abstract
- Co-evolved natural enemies provide sustainable and long-term control of numerous invasive insect pests, but the introduction of such enemies has declined sharply due to increasing regulations. In the absence of co-evolved natural enemies, native species may attack exotic invasive pests; however, they usually lack adaptations to control novel hosts effectively. We investigated the potential of two native pupal parasitoids, Pachycrepoideus vindemmiae and Trichopria drosophilae, to increase their developmental success on the invasive Drosophila suzukii. Replicated populations of the two parasitoids were subjected to 10 generations of laboratory selection on D. suzukii with Drosophila melanogaster serving as the co-evolved host. We assessed developmental success of selected and control lines in generations 0, 3, and 10. Changes in host preference, sex ratio, development time, and body size were measured to evaluate correlated responses with adaptation. Both parasitoid species responded rapidly to selection by significantly increasing their developmental success on the novel host within three generations, which remained constant for seven additional generations without further improvement. The generalist parasitoid species P. vindemmiae was able to reach similar developmental success as the control populations, while the performance of the more specialized parasitoid T. drosophilae remained lower on the novel than on the co-evolved host. There was no increase in preference towards the novel host over 10 generations of selection nor were there changes in development time or body size associated with adaptation in either parasitoid species. The sex ratio became less female-biased for both parasitoids after three generations of selection but rebounded in P. vindemmiae by generation 10. These results suggest that a few generations of selection may be sufficient to improve the performance of native parasitoids on invasive hosts, but with limits to the degree of improvement for managing invasive pests when exotic co-evolved natural enemies are not available.
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| 17. |
- Linder, Shelley, et al.
(författare)
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Non-target attack of the native stink bug, Podisus maculiventris by Trissolcus japonicus, comes with fitness costs and trade-offs
- 2023
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Ingår i: Biological Control. - : Elsevier BV. - 1049-9644. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Accidentally introduced parasitoids can provide biological control of the invasive pest they followed but could also pose a threat to native species if they are not specialists. Attack of native species could reduce the effectiveness of adventive natural enemies if it is accompanied by reduced fitness, and it may increase acceptance of non-target species. We tested how intermittent host shift and prolonged exposure to a non-target, native species Podisus maculiventris (Say) (Hemiptera: Pentatomidae) may affect the fitness and host acceptance of the egg parasitoid, Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae) that was co-introduced with the invasive Halyomorpha halys (Stål) (Hemiptera: Pentatomidae). In the first experiment, replicate parasitoid populations were reared either with or without a history of host switching over a 10-generation period between the native and the invasive stink bug that was followed by three generations of continuous reproduction on either host. In the second experiment, replicated populations were exposed for three continuous generations to either the native or invasive host. Occasional or prolonged reproduction on the native host did not increase acceptance and developmental success on the non-target species. Emergence rate of T. japonicus was consistently lower when it reproduced on the native stink bug. There was also a trade-off for the parasitoid, in terms of reduced emergence rate, when switching back to H. halys from the native host. These results suggest that host shifts to native species could reduce the effectiveness of T. japonicus at attacking H. halys, but the fitness costs may prevent significant non-target effects in nature.
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| 18. |
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| 19. |
- Sečenji, M, et al.
(författare)
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Differences in root functions during long-term drought adaptation : comparison of active gene sets of two wheat genotypes
- 2010
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Ingår i: Plant Biology. - : Wiley-Blackwell. - 1435-8603 .- 1438-8677. ; 12:6, s. 871-882
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Tidskriftsartikel (refereegranskat)abstract
- In an attempt to shed light on the role of root systems in differential responses of wheat genotypes to long-term water limitation, transcriptional differences between two wheat genotypes (Triticum aestivum L., cv. Plainsman V and landrace Kobomugi) were identified during adaptation to moderate water stress at the tillering stage. Differences in organ sizes, water-use efficiency and seed production were detected in plants grown in soil, and root functions were characterised by expression profiling. The molecular genetic background of the behaviour of the two genotypes during this stress was revealed using a cDNA macroarray for transcript profiling of the roots. During a 4-week period of moderate water deficit, a set of up-regulated genes displaying transiently increased expression was identified in young plantlets, mostly in the second week in the roots of Kobomugi, while transcript levels remained constantly high in roots of Plainsman V. These genes encode proteins with various functions, such as transport, protein metabolism, osmoprotectant biosynthesis, cell wall biogenesis and detoxification, and also regulatory proteins. Oxidoreductases, peroxidases and cell wall-related genes were induced significantly only in Plainsman V, while induction of stress- and defence-related genes was more pronounced in Kobomugi. Real-time qPCR analysis of selected members of the glutathione S-transferase gene family revealed differences in regulation of family members in the two genotypes and confirmed the macroarray results. The TaGSTZ gene was stress-activated only in the roots of Kobomugi.
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| 20. |
- van Steenbergen, Hanna W, et al.
(författare)
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EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis
- 2017
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:3, s. 491-496
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience.METHODS: The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics.RESULTS: The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined.CONCLUSIONS: A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established.
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